This is a Shannon Award providing partial support for the research projects that fall short of the assigned institute's funding range but are in the margin of excellence. The Shannon Award is intended to provide support to test the feasibility of the approach; develop further tests and refine research techniques; perform secondary analysis of available data sets; or conduct discrete projects that can demonstrate the PI's research capabilities or lend additional weight to an already meritorious application. The abstract below is taken from the original document submitted by the principal investigator. Although standard chemotherapy induces a remission in 70-90% of adult patients with acute lymphocytic leukemia (ALL), over half of such patients ultimately relapse and die of leukemic complications. Unfortunately, high dose chemotherapy followed by syngeneic or autologous bone marrow rescue fails to improve cure rates, suggesting that the leukemic cells in the majority of patients with ALL are inherently drug resistant. The substantially decreased relapse rates seen in ALL patients receiving HLA-identical allogeneic bone marrow transplantation (BMT) in first remission suggest that immunotherapy is an effective treatment of drug-resistant tumors, but allogeneic transplantation is limited by the toxicities of allogeneic graft-versus-host disease (GVHD) and the lack of a suitable donor in up to 70% of patients. The primary goal of this proposal is to develop strategies for the generation of an autologous antitumor immune response that is free of substantial clinical toxicities but nonetheless overcomes the phenomenon of drug resistance in patients with adult ALL. Two strategies are envisioned: (1) induction of an autoimmune syndrome, akin to autologous GVHD following BMT, by cyclosporine A (CsA) treatment following standard consolidation chemotherapy, and (2) active specific immunization with killed autologous tumor cells obtained from the patients at diagnosis. The specific aims of the proposal are to: 1) Determine if autoimmunity can be induced by treating ALL patients with CsA following consolidation chemotherapy and, if so, to assess whether in vivo administration of recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) affects CsA-induced autoimmunity. 2) Optimize conditions for generating cytotoxic T lymphocyte (CTL) responses to autologous tumor vaccines by: a) characterizing the regeneration of T lymphocyte and antigen presenting cell (APC) number and function after consolidation chemotherapy; b) assessing the effects of CsA and GM-CSF on self-tolerance induction and immune ontogeny following consolidation chemotherapy; and c) studying the immune responses to a recombinant hepatitis B vaccine at various intervals after consolidation chemotherapy. 3) Undertake pilot trials of leukemia cell acquisition, purification, and storage for later use as specific tumor vaccines.